Multiple sclerosis is a debilitating disease that is difficult to diagnose definitively, especially during the early stages of the disease. Multiple sclerosis is a common demyelinating disease of the central nervous system (CNS) that affects up to 0.1% of the Caucasian population of northern European descent. Multiple sclerosis is more common in women than men and generally begins between ages 20 and 40, but can develop at any age. Multiple sclerosis is generally viewed as an autoimmune syndrome directed against unidentified central nervous tissue antigens. The determination of susceptibility to multiple sclerosis development is complex and appears to be governed by both environmental and genetic factors. Some of the symptoms of multiple sclerosis are caused by damage to the myelin sheath, the protective covering that surrounds nerve cells. When this nerve covering is damaged, nerve impulses are slowed down or stopped. Ultimately, damage to the myelin sheath results in nerve damage. Nerve damage may be caused by inflammation that occurs when the body's immune cells attack the nervous system. Repeated episodes of inflammation can occur along any area of the brain and spinal cord, which is why the disease is often referred to as one characterized by symptoms and signs over time and space.
Multiple sclerosis is difficult to diagnose because the progress, severity and specific symptoms of multiple sclerosis are quite variable and unpredictable. There are no laboratory tests, symptoms or physical findings that can singly determine if a person has multiple sclerosis. The differential diagnosis of multiple sclerosis is quite varied and includes metabolic, genetic, oncologic, immunologic, and infectious disease assessment. Other diseases that may need to be considered in the differential diagnoses, depending on the clinical presentation, include: Acute disseminated encephalomyelitis, CNS vasculitis, Behçet disease, Sjögren syndrome, Sarcoid, neoplasms, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), Migrainous ischemia, Cerebrovascular disease, Progressive multifocal leukoencephalopathy, Inherited white matter diseases, effects of radiation therapy or drugs, CNS lymphoma, Lyme disease, HTLV-1 infection, CNS lupus, Mitochondrial encephalopathies, Antiphospholipid antibody syndrome, cerebral emboli, Thrombocytopenic purpura, Progressive multifocal leukoencephalopathy, Mycoplasma encephalopathy, Vitamin B12 deficiency, Paraneoplastic syndromes, Psychiatric syndromes (Rolak L A, Fleming J O. The Neurologist 2007; 13: 57-72).
Over the last twenty years, tests such as magnetic resonance imaging (MRI), examination of CSF, and evoked response testing have played an increasingly important role in the diagnostic process. In 2005, revised McDonald criteria for multiple sclerosis were published (Polman et al. Diagnostic Criteria for Multiple Sclerosis: 2005 Revisions to the “McDonald” Criteria. Ann Neurol. (2005) 58:840-846 and Polman et al. Ann Neurol (2011) 69:292-302). In addition to the traditional diagnostic tools, the revised criteria provide specific guidelines for using findings of MRI, cerebrospinal fluid analysis and visual evoked potentials to support a diagnosis of multiple sclerosis. However, even with these revised criteria, diagnosis of multiple sclerosis is still challenging and frequently takes several months or even years.
Rendering a conclusive diagnosis of multiple sclerosis on an expedited basis would be of great benefit to patients in light of the potential for recurrence of attacks and progression of the disease. Drugs for the treatment of multiple sclerosis are now available which slow or prevent progression of the disease in many patients, and an early diagnosis would, therefore, allow early intervention and could significantly improve the quality of life for many multiple sclerosis patients.
The citation of references herein shall not be construed as an admission that such is prior art to the present invention. Several publications and patent documents are referenced in this application in order to more fully describe the state of the art to which this invention pertains. The disclosure of each of these publications and documents is incorporated by reference herein.
Other features and advantages of the invention will be apparent from the detailed description, the drawings, and the claims.